Browse
Submit Data
Databases
API
Help

Dataset Information

17 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

SIX1/EYA1 are novel liver damage biomarkers in chronic hepatitis B and other liver diseases.

ABSTRACT:

Background

This study aimed to investigate the clinicopathological significance of sine oculis homeobox homolog 1 (SIX1) and eyes absent 1 (EYA1) in patients with chronic hepatitis B (CHB) and other liver diseases.

Methods

SIX1 and EYA1 levels were detected in human serum and liver tissues by enzyme linked immunosorbent assay (ELISA) and immunofluorescent staining method, respectively.

Results

The serum SIX1 and EYA1 levels in 313 CHB patients were 7.24±0.11 and 25.21±0.51 ng/mL, respectively, and these values were significantly higher than those in 33 healthy controls (2.84±0.15 and 13.11±1.01 ng/mL, respectively; P<0.05). Serum SIX1 and EYA1 levels were also markedly increased in patients with numerous other liver diseases, including liver fibrosis, hepatocellular carcinoma, fatty liver disease, alcoholic liver disease, fulminant hepatic failure, autoimmune liver disease, and hepatitis C, compared to the healthy controls (P<0.05). Dynamic observation of these proteins over time in 35 selected CHB patients revealed that SIX1 and EYA1 serum levels increased over an interval. Immunofluorescent staining revealed that both SIX1 and EYA1 were only expressed in hepatic stellate cells (HSCs), and their increased expression was evident in CHB liver tissue.

Conclusions

SIX1 and EYA1 are novel biomarkers of liver damage in patients of CHB and other liver diseases, with potential clinical utility.

SUBMITTER: Xu B

PROVIDER: S-EPMC8267256 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

SIX1 mutations cause branchio-oto-renal syndrome by disruption of EYA1-SIX1-DNA complexes.

Project description:Urinary tract malformations constitute the most frequent cause of chronic renal failure in the first two decades of life. Branchio-otic (BO) syndrome is an autosomal dominant developmental disorder characterized by hearing loss. In branchio-oto-renal (BOR) syndrome, malformations of the kidney or urinary tract are associated. Haploinsufficiency for the human gene EYA1, a homologue of the Drosophila gene eyes absent (eya), causes BOR and BO syndromes. We recently mapped a locus for BOR/BO syndrome (BOS3) to human chromosome 14q23.1. Within the 33-megabase critical genetic interval, we located the SIX1, SIX4, and SIX6 genes, which act within a genetic network of EYA and PAX genes to regulate organogenesis. These genes, therefore, represented excellent candidate genes for BOS3. By direct sequencing of exons, we identified three different SIX1 mutations in four BOR/BO kindreds, thus identifying SIX1 as a gene causing BOR and BO syndromes. To elucidate how these mutations cause disease, we analyzed the functional role of these SIX1 mutations with respect to protein-protein and protein-DNA interactions. We demonstrate that all three mutations are crucial for Eya1-Six1 interaction, and the two mutations within the homeodomain region are essential for specific Six1-DNA binding. Identification of SIX1 mutations as causing BOR/BO offers insights into the molecular basis of otic and renal developmental diseases in humans.

| S-EPMC419562 | biostudies-literature

Serum Glycopatterns as Novel Potential Biomarkers for Diagnosis of Acute-on-Chronic Hepatitis B Liver Failure.

Project description:Acute-on-chronic hepatitis B liver failure (ACHBLF) is an increasingly recognized distinct disease entity encompassing an acute deterioration of liver function in patients with cirrhosis, so little is known about the alterations of protein glycopatterns in serum with its development. We aimed to identify the alterations of serum glycopatterns in ACHBLF and probe the possibility of them as novel potential biomarkers for diagnosis of ACHBLF. As a result, there were 18 lectins (e.g., WFA, GSL-II, and PNA) to give significantly alterations of serum glycopatterns in ACHBLF compared with healthy controls (HC) (all p???0.0386). Meanwhile, among these lectins, there were 12 lectins (e.g., WFA, GAL-II, and EEL) also exhibited significantly alterations of serum glycopatterns in ACHBLF compared with HBV-infected chronic hepatitis (cHB) (all p???0.0252). The receiver-operating characteristic (ROC) curve analysis indicated there were 5 lectins (PHA-E?+?L, BS-I, ECA, ACA, and BPL) had the greatest discriminatory power for distinguishing ACHBLF and HC or cHB, respectively (all p???0.00136). We provided a new basic insight into serum glycopatterns in ACHBLF and investigated the correlation of alterations in serum glycopatterns as novel potential biomarkers for diagnosis of ACHBLF.

| S-EPMC5382696 | biostudies-literature

A Tbx1-Six1/Eya1-Fgf8 genetic pathway controls mammalian cardiovascular and craniofacial morphogenesis.

Project description:Shared molecular programs govern the formation of heart and head during mammalian embryogenesis. Development of both structures is disrupted in human chromosomal microdeletion of 22q11.2 (del22q11), which causes DiGeorge syndrome (DGS) and velo-cardio-facial syndrome (VCFS). Here, we have identified a genetic pathway involving the Six1/Eya1 transcription complex that regulates cardiovascular and craniofacial development. We demonstrate that murine mutation of both Six1 and Eya1 recapitulated most features of human del22q11 syndromes, including craniofacial, cardiac outflow tract, and aortic arch malformations. The mutant phenotypes were attributable in part to a reduction of fibroblast growth factor 8 (Fgf8), which was shown to be a direct downstream effector of Six1 and Eya1. Furthermore, we showed that Six1 and Eya1 genetically interacted with Fgf8 and the critical del22q11 gene T-box transcription factor 1 (Tbx1) in mice. Together, these findings reveal a Tbx1-Six1/Eya1-Fgf8 genetic pathway that is crucial for mammalian cardiocraniofacial morphogenesis and provide insights into the pathogenesis of human del22q11 syndromes.

| S-EPMC3069777 | biostudies-literature

SIX1 Activates STAT3 Signaling to Promote the Proliferation of Thyroid Carcinoma via EYA1.

Project description:As a critical member of the Retinal Determination Gene Network (RDGN), SIX1 has been regarded as a tumor promoter in various types of cancer. However, its role in papillary thyroid carcinoma (PTC) has never been investigated. In this study, thyroid carcinoma tissue microarray staining was employed to identify the expression patterns of SIX1 and its co-activator EYA1. Papillary thyroid cancer cell lines, BCPAP, and TPC-1 cells were used to investigate the potential mechanism of SIX1 in vitro and in vivo. Flow cytometry analysis, MTT assay, the growth curve assay, colony formation assay, EdU incorporation and xenograft assay were performed to demonstrate the role of SIX1 in the malignant change of PTC cells. Western blot and Real-time PCR were used to detect the interaction among the SIX1, EYA1, and STAT3 signaling. In comparison with normal tissue, high expressions of SIX1 and EYA1 were associated with a malignant tumor. Importantly, SIX1 strongly correlated with EYA1 in thyroid carcinoma tissue microarray. Functional assays indicated SIX1 increased EYA1 expression by stabilizing EYA1 at the post-transcriptional level. Besides, SIX1 promoted the proliferation and invasion of thyroid carcinoma via activation of STAT3 signaling and its downstream targets in an EYA1-dependent manner. SIX1 can integrate with EYA1 to contribute to PTC development via activation of the classical STAT3 signaling. These data suggested targeting the abnormal activation of the SIX1/EYA1 complex may represent a novel therapeutic strategy for advanced PTC patients.

| S-EPMC6933607 | biostudies-literature

Identification and Validation of Novel Serum Autoantibodies Biomarkers for Staging Liver Fibrosis in Patients With Chronic Hepatitis B.

Project description:Aim: Liver fibrosis monitoring is essential in patients with chronic hepatitis B (CHB). However, less robust, noninvasive diagnostic methods for staging liver fibrosis, other than liver biopsy, are available. Our previous study demonstrated a panel of cellular proteins recognized by autoantibodies that may have potential value in discrimination of CHB and liver cirrhosis. We aim to assess the diagnostic value of these serum autoantibodies for staging liver fibrosis. Methods: Candidate autoantigens were screened and assessed by microarray analysis in 96 healthy controls and 227 CHB patients with pre-treatment biopsy-proven METAVIR fibrosis score, comprising 69, 115, and 43 cases with S0-1, S2-3, and S4 stages, respectively. Autoantibodies with potential diagnostic value for staging liver fibrosis were verified by enzyme-linked immunosorbent assays (ELISA). Receiver operating characteristic curve was conducted to evaluate autoantibody performance. Results: Microarray analysis identified autoantigens CENPF, ACY1, HSPA6, and ENO1 with potential diagnostic value for liver fibrosis staging, among which CENPF and ACY1 were validated using ELISA. CENPF and ACY1 autoantibodies had area under the curve values of 0.746 and 0.685, 58.14 and 74.42% sensitivity, and 88.41 and 60.87% specificity, respectively, for discriminating liver fibrosis stages S4 and S0-1. The prevalence of CENPF and ACY1 autoantibodies was not correlated with age, sex or level of inflammation. Conclusions: Autoimmune responses may be elicited during progression of liver fibrosis, and serum autoantibodies may be a valuable biomarker for staging liver fibrosis deserving of further study.

| S-EPMC8764302 | biostudies-literature

Eya1 and Six1 promote neurogenesis in the cranial placodes in a SoxB1-dependent fashion.

Project description:Genes of the Eya family and of the Six1/2 subfamily are expressed throughout development of vertebrate cranial placodes and are required for their differentiation into ganglia and sense organs. How they regulate placodal neurogenesis, however, remains unclear. Through loss of function studies in Xenopus we show that Eya1 and Six1 are required for neuronal differentiation in all neurogenic placodes. The effects of overexpression of Eya1 or Six1 are dose dependent. At higher levels, Eya1 and Six1 expand the expression of SoxB1 genes (Sox2, Sox3), maintain cells in a proliferative state and block expression of neuronal determination and differentiation genes. At lower levels, Eya1 and Six1 promote neuronal differentiation, acting downstream of and/or parallel to Ngnr1. Our findings suggest that Eya1 and Six1 are required for both the regulation of placodal neuronal progenitor proliferation, through their effects on SoxB1 expression, and subsequent neuronal differentiation.

| S-EPMC2671077 | biostudies-literature

Inflammatory and cardiovascular diseases biomarkers in chronic hepatitis C virus infection: A review.

Project description:Hepatitis C virus (HCV) infects 180 million people worldwide and over 4 million people in the United States. HCV infection is a major cause of chronic liver disease and is recognized as a risk factor for clinical cardiovascular disease (CVD). Many studies have shown increased prevalence of cardiac and inflammatory biomarkers in patients with chronic HCV infection (CHC), and though these markers may be used to risk stratify people for cardiac disease in the general population their role in the HCV population is unknown. Patients with CHC have elevated cardiac and inflammatory biomarkers compared to noninfected controls which may play a role in CVD risk stratification. We undertook a systematic review of inflammatory and cardiac biomarkers in people with HCV infection with a focus on the effect of CHC on serum levels of these markers and their utility as predictors of CVD in this population. Medline, EMBASE, and Cochrane databases were searched for relevant articles until June 2019. A total of 2430 results were reviewed with 115 studies included. Our review revealed that HCV infection significantly alters serum levels of markers of inflammation, endothelial function, and cardiac dysfunction prior to HCV treatment, and some of which may change in response to HCV therapy. Current risk stratification tools for development of CVD in the general population may not account for the increased inflammatory markers that appear to be elevated among HCV-infected patients contributing to increased CVD risk.

| S-EPMC7068107 | biostudies-literature

Inflammation and fibrosis in chronic liver diseases including non-alcoholic fatty liver disease and hepatitis C.

Project description:At present chronic liver disease (CLD), the third commonest cause of premature death in the United Kingdom is detected late, when interventions are ineffective, resulting in considerable morbidity and mortality. Injury to the liver, the largest solid organ in the body, leads to a cascade of inflammatory events. Chronic inflammation leads to the activation of hepatic stellate cells that undergo trans-differentiation to become myofibroblasts, the main extra-cellular matrix producing cells in the liver; over time increased extra-cellular matrix production results in the formation of liver fibrosis. Although fibrogenesis may be viewed as having evolved as a "wound healing" process that preserves tissue integrity, sustained chronic fibrosis can become pathogenic culminating in CLD, cirrhosis and its associated complications. As the reference standard for detecting liver fibrosis, liver biopsy, is invasive and has an associated morbidity, the diagnostic assessment of CLD by non-invasive testing is attractive. Accordingly, in this review the mechanisms by which liver inflammation and fibrosis develop in chronic liver diseases are explored to identify appropriate and meaningful diagnostic targets for clinical practice. Due to differing disease prevalence and treatment efficacy, disease specific diagnostic targets are required to optimally manage individual CLDs such as non-alcoholic fatty liver disease and chronic hepatitis C infection. To facilitate this, a review of the pathogenesis of both conditions is also conducted. Finally, the evidence for hepatic fibrosis regression and the mechanisms by which this occurs are discussed, including the current use of antifibrotic therapy.

| S-EPMC6962431 | biostudies-literature

Canonical Wnt signaling modulates Tbx1, Eya1, and Six1 expression, restricting neurogenesis in the otic vesicle.

Project description:To understand the mechanism by which canonical Wnt signaling sets boundaries for pattern formation in the otic vesicle (OV), we examined Tbx1 and Eya1-Six1 downstream of activated beta-catenin. Tbx1, the gene for velo-cardio-facial syndrome/DiGeorge syndrome (VCFS/DGS), is essential for inner ear development where it promotes Bmp4 and Otx1 expression and restricts neurogenesis. Using floxed beta-catenin gain-of-function (GOF) and loss-of-function (LOF) alleles, we found Tbx1 expression was down-regulated and maintained/enhanced in the two mouse mutants, respectively. Bmp4 was ectopically expressed and Otx1 was lost in beta-catenin GOF mutants. Normally, inactivation of Tbx1 causes expanded neurogenesis, but expression of NeuroD was down-regulated in beta-catenin GOF mutants. To explain this paradox, Eya1 and Six1, genes for branchio-oto-renal (BOR) syndrome were down-regulated in the OV of beta-catenin GOF mutants independently of Tbx1. Overall, this work helps explain the mechanism by which Wnt signaling modulates transcription factors required for neurogenesis and patterning of the OV.

| S-EPMC2987613 | biostudies-literature

Omics-derived hepatocellular carcinoma risk biomarkers for precision care of chronic liver diseases.

Project description:Precise hepatocellular carcinoma (HCC) risk prediction will play increasingly important roles with the contemporary HCC etiologies, that is, non-alcoholic fatty liver disease and resolved hepatitis C virus infection. Because the HCC incidence rate in this emerging patient population is relatively low (~1% per year), identification of a subset of patients at the highest risk is critical to concentrate the effort and resources of regular HCC screening to those who most need it. Omics profiling has been derived using several candidate HCC risk biomarkers, which could refine HCC screening by enabling individual risk-based personalized or risk-stratified patient management. Various types of biomolecules have been explored as sources of information to predict HCC risk at various time horizons. Germline DNA polymorphisms likely reflect race/ethnicity- and/or etiology-specific susceptibility to HCC development or chronic liver disease progression toward carcinogenesis. Transcriptomic dysregulations in the diseased liver capture functional molecular status supporting oncogenesis such as inflammatory pathway and myofibroblast activation. Circulating nucleic acids, proteins, and metabolites could serve as less-invasive measures of molecular HCC risk. Characterization of gut microbiota could also inform HCC risk estimation. Each biomarker could have its niche of clinical application depending on logistics of use, performance, and costs with a goal to eventually improve patient prognosis as a part of the whole algorithm of chronic liver disease management.

| S-EPMC8318383 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data